Mechanical loading during daily activities plays a critical role in the onset and progression of knee osteoarthritis (OA). Taking advantage of the rich quantitative MRI dataset acquired through the parent study (AR R0146905-11), this project utilizes a multi-scale approach towards understanding the knee OA disease process by evaluating cartilage compositional changes, joint contact mechanics, whole-body neuromuscular dynamics and functional performance. One hundred-five subjects with and without knee OA will undergo kinematic-MRI, neuromuscular control testing during functional tasks, metrics of functional performance, and quantitative MR for cartilage and meniscus composition. Both cross-sectional (OA vs. controls) and longitudinal (baseline, 1- year, 2-year, and 3-year follow-up) aims are proposed. With the addition of in-vivo articular contact mechanics and neuromuscular patterns, the dataset will become extremely comprehensive giving an unparalleled ability to look at multiple metrics affecting incidence and progression in knee OA. It is hypothesized that the resulting combined metrics, across scales from tissue composition to function, will provide stronger biomarkers for early detection and progression prognosis of the disease. This knowledge will be directly translatable to the clinic since neuromuscular factors like strength, movement, and muscle activation are modifiable through targeted orthotic and rehabilitation interventions;and structural factors like malalignment or abnormal articular contact mechanics may be influenced through surgical interventions. Specific Aim 1: A) To quantify differences in articular contact mechanics using kinematic MR in controls and subjects with knee OA;and to establish the correlation of articular contact mechanics with metrics from cartilage and meniscus T1A and T2 relaxation times, morphological grades, radiographic and functional measures. B) To quantify differences in neuromuscular control in controls and subjects with knee OA;and to determine the relationship between neuromuscular control during walking and articular contact mechanics, cartilage and meniscus T1A and T2 relaxation times, morphological grades, radiographic and functional measures. Specific Aim 2: A) To determine the longitudinal change over three years in articular contact mechanics in controls and subjects with knee OA;and to determine the longitudinal change over three years in neuromuscular control during walking in controls and subjects with knee OA. B) To determine the predictive capability of baseline articular contact mechanics and neuromuscular control at determining disease progression. PUBLIC HEALTH RELEVANCE: This study will analyze how common daily activities like walking and climbing stairs relate to pressure on the knee and health of knee cartilage. Once we determine healthy and unhealthy ways that people move during common activities, we can develop more effective care for people who might get, and those who already have, knee osteoarthritis.